Retinitis Pigmentosa (RP) is an inherited disease of the eye that robs its victims of vision. The loss of vision is caused by the degeneration of the rods and cones of the retina while other cells in the retina remain alive. RD is a relatively rare disease, affecting approximately 100,000 people in the US. Approximately 20% of children in schools for the blind suffer from RP. Clearly, the disastrous consequences of RP provide justification for intense research into the causes and potential therapies. Due to the polygenic nature of RP, it does not lend itself to gene therapy or targeted therapeutics. Although some successes in vision restoration using gene therapy have been reported, it is highly unlikely that such therapy will be approved and adopted by the medical community in the near future. An alternative approach to vision restoration for patients with RP, which does not involve gene therapy, is proposed in this Phase I SBIR application where the remaining cells in the damaged retina are made into photosensitive cells using small molecules called "photoswitches". Photoswitches could, in theory, provide resolution approximately a thousand times greater than that of competing video camera prosthetics and will be far less invasive. The four Specific Aims for the first steps along the pathway to an approved therapeutic are (1) Determine which of the many cells in the retina are rendered light-sensitive by the injection of photoswitches into the eyes of blind mice;(2) Demonstrate light-sensitivity in intact mutant blind mice using non-invasive electrophysiological approaches;(3) Demonstrate light-dependent behavior in genetically blind mice after photoswitch treatment;and (4) Determine the optimal parameters for maintaining light-sensitivity in mutant blind mice. The successful completion of this feasibility project will provide justification for the further pursuit of this therapeutic approach to blindness. PUBLIC HEALTH RELEVANCE: Retinitis Pigmentosa (RP) is an inherited disease of the eye that robs its victims of vision. While RD is a relatively rare disease, affecting approximately 100,000 people in the US, approximately 20% of children in schools for the blind suffer from RP. Clearly, the disastrous consequences of RP provide justification for intense research into the causes and potential therapies. Photoswitch Biosciences has developed a technology that has the potential to make healthy cells in the eye into cells that can receive and decode light, restoring sight to sufferers of RP.